What does COVID-19 mean for the Diamond Blackfan Anemia community?

Frequently Asked Questions

 

A few key points:

1 – Coronavirus disease or COVID-19 is caused by a novel coronavirus (meaning that this virus has never infected humans before and there is no immunity in the general population). Coronaviruses are a large family of viruses that are common in people and many different species of animals. Rarely, animal coronaviruses can infect people and then spread among people such as with the Middle Eastern Respiratory Syndrome (MERS-CoV) and the Severe Acute Respiratory Syndrome (SARS-CoV), and now with this new virus, named SARS-CoV-2 that is commonly known as COVID-19; the name used in the following questions/answers. 

2 – The answers provide general knowledge about the novel coronavirus disease called COVID19. The information comes from our growing clinical experience and from reliablesources such as the CDC and NIH and others.

3 – If you have questions about possible symptoms of COVID-19 infection that you or your child are experiencing, please speak to your or your child’s provider.

4 – Reported COVID-19 have ranged from mild symptoms to severe illness and death in the general population.

5 – Symptoms may appear 2-14 days after exposure and usually include fever, cough, shortness of breath and muscle aches. Some patients may be without any symptoms (asymptomatic) and some will have worsening symptoms and require hospitalization.

6 – Do not take any medications on your own to prevent or treat COVID-19. There are no medications that are proven to work to prevent COVID-19 infection (prophylactically) at this time and the medical community is still learning what the best regimen is to treat COVID-19.

7 – Until there are full testing capabilities and a vaccine there may be another wave of infection. For this reason the DBAR would like to gather information on any DBA patient infected with COVID-19 so we can accumulate a list of symptoms, risk factors and outcomes. If you or your child with DBA have been diagnosed with COVID-19, please complete the COVID-19 survey or call/email the DBAR.

 

Topic 1: Questions regarding which patients with DBA are considered “high risk”

Which DBA patients are considered to be at higher risk than the general public with respect to contracting and succumbing to COVID-19?


In the general population, older age, obesity, high blood pressure, diabetes, pre-existing lung disease, compromised immune system and/or cardiac disease have been risk factors for getting very sick with COVID-19. Newer data are indicating that African Americans may also have an increased risk. We do not have any data for DBA patients so this question cannot be answered precisely at this time. With regards to contracting the virus those patients on high-dose steroids and patients with known immune deficiency may be at higher risk. We also theorize that patients with high iron burdens, in particular with cardiac disease from iron overload or with diabetes from iron overload, as well as older patients may be at higher risk of COVID-19 complications.




Is a DBA patient on low dose prednisone with a normal WBC count at greater risk than a person without DBA? Is there a maintenance dose of steroids below which they are no longer considered immunocompromised?


The physicians in DBA community considers the maximal dose of steroids should be less than 0.5 mg/kg/day or 1 mg/kg every other day. This dose is not considered immunosuppressive and, in fact, at these doses, patients can receive live virus vaccines without increased risk.




If a DBA patient is in remission, would he/she still be considered at a higher risk because he/she has an underlying condition?


In general DBA patients are not immune suppressed so most patients may be considered at regular risk. However, this depends on the dose of steroids if the patient is steroid dependent. It also depends on the severity of the iron overload if the patient is transfusion dependent, and the patient’s overall health. This includes whether the patient has endocrinologic problems such as diabetes or decreased thyroid function, or decreased heart function. Each patient has their own individual risk profile that needs to be taken into consideration.




Does being iron overloaded or chelating put a DBA patient at higher risk?


Chelation does not appear to put a patient at any risk for viral infection. However, iron overload can put you at risk for certain bacterial infections and can put you at high risk for endocrine disorders like diabetes, low thyroid hormone, a poor stress response, heart failure, and heart rhythm abnormalities. Individual risk profiles must be taken into consideration.




Many DBA patients never had T-cell or IGG studies done. If a patient hasn’t had those tests, should it be assumed that he/she is immunocompromised just to be safe?


No – DBA is, in general, NOT an immune suppressive disease. Patients with a few RP mutations may have immune suppression. A history of infections should be considered in assessing an individual risk profile. If the patient is on low steroid dose or has low iron burden, then they are not in general significantly immunocompromised.

Some DBA patients may havelow white blood cell (WBC) counts and low neutrophil counts (also called neutropenia). Most patients with DBA do not have severe clinical neutropenia. This means that usually if the patient develops a bacterial infection the WBC and neutrophil count will increase or will functionally be able to fight the bacterial infection. Also having neutropenia does not make a person immunocompromised. Your immune system mostly comes from your lymphocytes. Our body uses lymphocytes to fight viruses so the neutropenia in some DBA patients should not make patients more susceptible to COVID-19.





Topic 2: Taking Precautions against COVID-19

Which DBA patients are considered to be at higher risk than the general public with respect to contracting and succumbing to COVID-19?


In the general population, older age, obesity, high blood pressure, diabetes, pre-existing lung disease, compromised immune system and/or cardiac disease have been risk factors for getting very sick with COVID-19. Newer data are indicating that African Americans may also have an increased risk. We do not have any data for DBA patients so this question cannot be answered precisely at this time. With regards to contracting the virus those patients on high-dose steroids and patients with known immune deficiency may be at higher risk. We also theorize that patients with high iron burdens, in particular with cardiac disease from iron overload or with diabetes from iron overload, as well as older patients may be at higher risk of COVID-19 complications.




Is a DBA patient on low dose prednisone with a normal WBC count at greater risk than a person without DBA? Is there a maintenance dose of steroids below which they are no longer considered immunocompromised?


The physicians in DBA community considers the maximal dose of steroids should be less than 0.5 mg/kg/day or 1 mg/kg every other day. This dose is not considered immunosuppressive and, in fact, at these doses, patients can receive live virus vaccines without increased risk.




If a DBA patient is in remission, would he/she still be considered at a higher risk because he/she has an underlying condition?


In general DBA patients are not immune suppressed so most patients may be considered at regular risk. However, this depends on the dose of steroids if the patient is steroid dependent. It also depends on the severity of the iron overload if the patient is transfusion dependent, and the patient’s overall health. This includes whether the patient has endocrinologic problems such as diabetes or decreased thyroid function, or decreased heart function. Each patient has their own individual risk profile that needs to be taken into consideration.




Does being iron overloaded or chelating put a DBA patient at higher risk?


Chelation does not appear to put a patient at any risk for viral infection. However, iron overload can put you at risk for certain bacterial infections and can put you at high risk for endocrine disorders like diabetes, low thyroid hormone, a poor stress response, heart failure, and heart rhythm abnormalities. Individual risk profiles must be taken into consideration.




Many DBA patients never had T-cell or IGG studies done. If a patient hasn’t had those tests, should it be assumed that he/she is immunocompromised just to be safe?


No – DBA is, in general, NOT an immune suppressive disease. Patients with a few RP mutations may have immune suppression. A history of infections should be considered in assessing an individual risk profile. If the patient is on low steroid dose or has low iron burden, then they are not in general significantly immunocompromised.

Some DBA patients may havelow white blood cell (WBC) counts and low neutrophil counts (also called neutropenia). Most patients with DBA do not have severe clinical neutropenia. This means that usually if the patient develops a bacterial infection the WBC and neutrophil count will increase or will functionally be able to fight the bacterial infection. Also having neutropenia does not make a person immunocompromised. Your immune system mostly comes from your lymphocytes. Our body uses lymphocytes to fight viruses so the neutropenia in some DBA patients should not make patients more susceptible to COVID-19.





Topic 3: Questions about transfusion dependent DBA patients

Which DBA patients are considered to be at higher risk than the general public with respect to contracting and succumbing to COVID-19?


In the general population, older age, obesity, high blood pressure, diabetes, pre-existing lung disease, compromised immune system and/or cardiac disease have been risk factors for getting very sick with COVID-19. Newer data are indicating that African Americans may also have an increased risk. We do not have any data for DBA patients so this question cannot be answered precisely at this time. With regards to contracting the virus those patients on high-dose steroids and patients with known immune deficiency may be at higher risk. We also theorize that patients with high iron burdens, in particular with cardiac disease from iron overload or with diabetes from iron overload, as well as older patients may be at higher risk of COVID-19 complications.




Is a DBA patient on low dose prednisone with a normal WBC count at greater risk than a person without DBA? Is there a maintenance dose of steroids below which they are no longer considered immunocompromised?


The physicians in DBA community considers the maximal dose of steroids should be less than 0.5 mg/kg/day or 1 mg/kg every other day. This dose is not considered immunosuppressive and, in fact, at these doses, patients can receive live virus vaccines without increased risk.




If a DBA patient is in remission, would he/she still be considered at a higher risk because he/she has an underlying condition?


In general DBA patients are not immune suppressed so most patients may be considered at regular risk. However, this depends on the dose of steroids if the patient is steroid dependent. It also depends on the severity of the iron overload if the patient is transfusion dependent, and the patient’s overall health. This includes whether the patient has endocrinologic problems such as diabetes or decreased thyroid function, or decreased heart function. Each patient has their own individual risk profile that needs to be taken into consideration.




Does being iron overloaded or chelating put a DBA patient at higher risk?


Chelation does not appear to put a patient at any risk for viral infection. However, iron overload can put you at risk for certain bacterial infections and can put you at high risk for endocrine disorders like diabetes, low thyroid hormone, a poor stress response, heart failure, and heart rhythm abnormalities. Individual risk profiles must be taken into consideration.




Many DBA patients never had T-cell or IGG studies done. If a patient hasn’t had those tests, should it be assumed that he/she is immunocompromised just to be safe?


No – DBA is, in general, NOT an immune suppressive disease. Patients with a few RP mutations may have immune suppression. A history of infections should be considered in assessing an individual risk profile. If the patient is on low steroid dose or has low iron burden, then they are not in general significantly immunocompromised.

Some DBA patients may havelow white blood cell (WBC) counts and low neutrophil counts (also called neutropenia). Most patients with DBA do not have severe clinical neutropenia. This means that usually if the patient develops a bacterial infection the WBC and neutrophil count will increase or will functionally be able to fight the bacterial infection. Also having neutropenia does not make a person immunocompromised. Your immune system mostly comes from your lymphocytes. Our body uses lymphocytes to fight viruses so the neutropenia in some DBA patients should not make patients more susceptible to COVID-19.





Topic 4: Questions about steroid dependent DBA patients

Should we refrain from starting an initial steroid trial during this time (within the next 6 months)? I have heard that steroids can make the immune system weaker.


It may be wise to refrain from starting high dose steroids until the COVID-19 risk decreases in your area. Generally at one year of age, the patient receives the routine live vaccines. About one month later the patient undergoes a bone marrow aspirate and biopsy, if they have not had it done as a baseline before, and then starts a trial with steroids. At this time many institutions are not doing routine procedures so bone marrow exams cannot be done. Also patients who start high dose steroids require ER visits and/or admission for any fever and will need an increase number of visits to the clinic to monitor the side effects of the steroids. Extending the duration of transfusions for a few months until the COVID-19 risk has decreased is not dangerous.




Should we be concerned about the steroid stock?


There is no reported risk of Prednisone or Prednisolone shortage at this time.




I have read that giving steroids can make COVID-19 worse. If my child gets it, should we not do the steroid stress dose protocol like we normally do for illness?


Steroids have been used to treat the lung inflammation with COVID-19 so there should not be fear to use steroids. Stress dose steroids when a steroid dependent patient gets a fever can be vital. In fact adrenal insufficiency should always be treated in the face of a fever as adrenal insufficiency can develop into a critical situation. Both chronic steroid use and iron overload can contribute to adrenal insufficiency.




Are patients with secondary adrenal insufficiency at higher risk of severe disease or complications with COVID-19?


Adrenal insufficiency must be diagnosed and treated immediately in the face of high fevers associated with any infections, including COVID-19. Adrenal insufficiency in and of itself is a risk factor during any stress.





Topic 5: Questions about DBA patients in remission and transplant patients

Which DBA patients are considered to be at higher risk than the general public with respect to contracting and succumbing to COVID-19?


In the general population, older age, obesity, high blood pressure, diabetes, pre-existing lung disease, compromised immune system and/or cardiac disease have been risk factors for getting very sick with COVID-19. Newer data are indicating that African Americans may also have an increased risk. We do not have any data for DBA patients so this question cannot be answered precisely at this time. With regards to contracting the virus those patients on high-dose steroids and patients with known immune deficiency may be at higher risk. We also theorize that patients with high iron burdens, in particular with cardiac disease from iron overload or with diabetes from iron overload, as well as older patients may be at higher risk of COVID-19 complications.




Is a DBA patient on low dose prednisone with a normal WBC count at greater risk than a person without DBA? Is there a maintenance dose of steroids below which they are no longer considered immunocompromised?


The physicians in DBA community considers the maximal dose of steroids should be less than 0.5 mg/kg/day or 1 mg/kg every other day. This dose is not considered immunosuppressive and, in fact, at these doses, patients can receive live virus vaccines without increased risk.




If a DBA patient is in remission, would he/she still be considered at a higher risk because he/she has an underlying condition?


In general DBA patients are not immune suppressed so most patients may be considered at regular risk. However, this depends on the dose of steroids if the patient is steroid dependent. It also depends on the severity of the iron overload if the patient is transfusion dependent, and the patient’s overall health. This includes whether the patient has endocrinologic problems such as diabetes or decreased thyroid function, or decreased heart function. Each patient has their own individual risk profile that needs to be taken into consideration.




Does being iron overloaded or chelating put a DBA patient at higher risk?


Chelation does not appear to put a patient at any risk for viral infection. However, iron overload can put you at risk for certain bacterial infections and can put you at high risk for endocrine disorders like diabetes, low thyroid hormone, a poor stress response, heart failure, and heart rhythm abnormalities. Individual risk profiles must be taken into consideration.




Many DBA patients never had T-cell or IGG studies done. If a patient hasn’t had those tests, should it be assumed that he/she is immunocompromised just to be safe?


No – DBA is, in general, NOT an immune suppressive disease. Patients with a few RP mutations may have immune suppression. A history of infections should be considered in assessing an individual risk profile. If the patient is on low steroid dose or has low iron burden, then they are not in general significantly immunocompromised.

Some DBA patients may havelow white blood cell (WBC) counts and low neutrophil counts (also called neutropenia). Most patients with DBA do not have severe clinical neutropenia. This means that usually if the patient develops a bacterial infection the WBC and neutrophil count will increase or will functionally be able to fight the bacterial infection. Also having neutropenia does not make a person immunocompromised. Your immune system mostly comes from your lymphocytes. Our body uses lymphocytes to fight viruses so the neutropenia in some DBA patients should not make patients more susceptible to COVID-19.





Topic 6: Questions about COVID-19 treatment/vaccines

Ifa patient with DBA gets COVID-19, can we be given some of the possible treatment options mentioned in the media such as hydroxychloroquine (Plaquenil®), azithromycin (Zithromax®), antibodies from plasma, or anything else? Are there any contradictions to these treatments specific to DBA or our treatments?


You or your child’s physician will make treatment choices as he/she is aware of your individual risk profile. Recommendations regarding treatment are changing as more data are available and your provider will know what is available and what is being used in clinical trials at your medical center.

The medications used to treat COVID-19 include hydroxychloroquine (Plaquenil®) with and without azithromycin (Zithromax®). Most recently azithromycin has been discontinued in combination as newer data demonstrate no increase in effectiveness with potentially increased toxicity. There are reports of cardiac arrhythmias with the two-drug combination. Chloroquine and hydroxychloroquine must be used cautiously in all patients and especially in DBA patients with a history of cardiac iron overload and/or cardiac arrhythmias. Treatment should be done in consultation with cardiology for transfusion dependent DBA patients with iron overload. These drugs should likely only be used in patients with DBA who are hospitalized and can be monitored closely.

Another drug being used includes the antiviral agent remdesivir which was developed for patients with Ebola virus, another coronavirus. This drug can be obtained for adults on a clinical study only and for children by compassionate release only.

For theoretical reasons, known anti-inflammatory, also called anti-cytokine, drugs are being given for the inflammation seen with COVID-19 pneumonia. These drugs suppress the immune system and include anakinra and tocilizumab.

None of these drugs have known contraindications for patients with DBA except as previously mentioned with regards to iron overload of the heart and certain endocrine issues. However there are no specific data on efficacy and risk in DBA either. These medications should be administered by your or your child’s physician in consultation with cardiology, endocrinology and infectious disease experts.

The use of convalescent serum therapy, also called plasma therapy is presently under investigation. People who recover from a viral infection develop antibodies to that virus that circulate in the plasma. There is some evidence that in COVID-19 these antibodies can neutralize the virus. Convalescent plasma involves extracting virus-fighting antibodies from the plasma of individuals who have recovered from COVID-19 and then, through transfusion, giving those antibodies to people who are currently sick with COVID-19. Each donor can provide enough plasma for 2 to 4 patients. Researchers hope this treatment will help cure people who are too sick to recover on their own or help patients recover before they get too sick. This therapy has been used in the past for measles and polio. Clinical trials should begin by May 1stat Johns Hopkins and open throughout the country in more institutions as well.




Do you know if the vaccines that are being worked on are live or dead vaccines? If a vaccine becomes available in the future will DBA patients be able to receive it? How about for patients on steroids?


The COVID-19 vaccine will be a killed vaccine and should be safe for all patients, similar to the regular flu shot. It should be safe for patients on steroids as well although its efficacy in DBA will need to be studied. The DBAR will mount such a study, if feasible.




Researchers are looking into the BCG vaccine, a well-known vaccine for tuberculosis, as a possible COVID-19 prophylactic that may lend a layer of protection. What should DBA patients know about that possibility? Should they get it if they can?


BCG is a live vaccine for tuberculosis disease. It boosts the immune system to make antibodies against tuberculosis and may help patients fight some other respiratory infections. It is given in countries where tuberculosis is still prevalent. There are two new studies in Australia and the Netherlands to vaccinate health care workers with the BCG vaccine to see if it gives them any protection against COVID-19. A study may open in the US out of the Massachusetts General Hospital in Boston. This is not something that should be considered in any patients outside of these clinical settings.




In a few months when the eminent threat of this virus has died down, many patients with DBA will still be at a higher risk than the general population. Should we consider continuing to work from home or home schooling until proven treatments and/or a vaccine are available?


We have no evidence that DBA alone places patients at higher risk of getting COVID-19 or at higher risk of having a worse outcome. This all remains to be seen. The severity of your disease, your current steroid dose and your iron burden may be risk factors so each patient with DBA needs to be assessed as an individual. Hopefully people will only be permitted to return to work when it is safe to do so. This will depend on the ability to monitor the infection (the amount of virus present in the population) and determine those who maybe safe to return to work or school because they were already infected. As for working from home and returning to school, this will depend upon the CDC and each state’s Department of Health guidelines and the patient’s individual risk profile.




When will it be safe for a steroid dependent DBA child to return to school?


In general DBA patients should be able to return to school when the general population returns to school.